研究概要
所有接受该免疫治疗的患者均完成了至少 2 年的随访,且无 HCC 复发证据(中位随访 96 个月 [范围 17-121 个月])。
中文摘要
肝细胞癌(HCC)合并肝硬化患者可选择肝移植(LT)作为有效治疗,但肿瘤复发是限制长期生存的关键因素。为预防复发,我们开展了死亡供者肝源性自然杀伤(NK)细胞过继输注的Ⅰ期研究。研究从供肝灌注液中分离肝脏NK细胞,并在体外用IL-2刺激;患者在肝移植后3~5天接受静脉输注。共治疗18名肝移植受者,未发生严重的细胞输注相关不良事件或急性排斥反应。1名患者因病理检查显示为肉瘤而非HCC退出研究。所有接受该免疫治疗的患者均完成至少2年随访,未见HCC复发;中位随访96个月(范围17~121个月)。在17名患者中有9名(52.9%)的病理特征超出米兰标准的情况下,肝脏NK细胞输注可能有助于预防肝移植后HCC复发。这是首次在人体中使用死亡供者肝源性NK细胞预防肝移植后HCC复发的免疫治疗研究。该疗法耐受性良好,且研究中未观察到肝移植后HCC复发。临床试验注册:ClinicalTrials.gov,NCT01147380;注册日期:2010年6月17日。
展开英文摘要原文
Liver transplantation (LT) is a viable treatment option for cirrhosis patients with hepatocellular carcinoma (HCC). However, recurrence is the rate-limiting factor of long-term survival. To prevent this, we conducted the phase I study of the adoptive transfer of deceased donor liver-derived natural killer (NK) cells. Liver NK cells were extracted from donor liver graft perfusate and were stimulated in vitro with IL-2. The patient received an intravenous infusion of NK cells 3-5 days after LT. Eighteen LT recipients were treated. There were no severe cell infusion-related adverse events or acute rejection episodes. One patient withdrew from the study because the pathological observation revealed sarcoma instead of HCC. All patients who received this immunotherapy completed the follow-up for at least 2 years without evidence of HCC recurrence (median follow-up, 96 months [range, 17-121 months]). Considering that 9 (52.9%) of the 17 patients pathologically exceeded the Milan criteria, liver NK cell infusion is likely to be useful for preventing HCC recurrence after LT. This is the first-in-human immunotherapy study using deceased donor liver-derived NK cells to prevent HCC recurrence after LT. This treatment was well tolerated and resulted in no HCC recurrence after LT.Clinical trial registration www.clinicaltrials.gov ; NCT01147380; registration date: June 17, 2010.
论文信息
- 作者
- Ohira M、Hotta R、Tanaka Y、Matsuura T、Tekin A、Selvaggi G、Vianna R、Ricordi C
- 第一作者单位
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.Japan
- 通讯作者单位
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. hohdan@hiroshima-u.ac.jp.Japan
- 期刊
- Cancer immunology, immunotherapy : CII2022 Mar